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Abstract

Grant Number:	1R43GM069136-01
PI Name:	HOUSTON, L L.
PI Email:	lhouston@arizeke.com
PI Title:	MANAGING DIRECTOR
Project Title:	Affinity Maturation and Transcytosis

Abstract: DESCRIPTION (provided by applicant): We have discovered a new method for administering proteins to the pulmonary system by a noninvasive technique using a receptor-mediated process. Because injection is invasive and not well accepted by patients, or the medical community, this method should be well received after we develop an aerosol formulation to deliver proteins. Our method using aerosol delivery can be applied to nearly any protein and can serve billion dollar markets. Large proteins do not normally cross-epithelial barriers (i.e., lung and intestine); therefore, they are parenterally administered to patients. Polymeric immunoglobulin receptor (plgR) specifically moves by transcytosis large immunoglobulins, such as dimeric IgA (350,000 MW) and pentameric IgM (900,000 MW), across the epithelial cell barrier into the lumen of lung. This process of receptor-mediated transcytosis is capable of transporting large amounts (grams of protein per day) of IgA in an adult human in order to fight harmful agents in the airways and intestines. Arizeke has discovered and demonstrated in animals that the transcytosis route could be used in reverse to transport drugs from the apical surface to the basolateral surface (i.e., from the lumen of lung to the bloodstream). To optimize the transport of single chain Fv (a sFv that binds to polymeric immunoglobulin receptor) across the epithelial cell barrier, we will optimize the binding properties of the sFv, using phage display affinity maturation techniques. Once this has been achieved, Arizeke will genetically fuse the sFv to therapeutic protein domains and deliver this new drug entity by aerosol formulations to patients

Thesaurus Terms:
biotherapeutic agent, drug delivery system, immunoglobulin structure, method development, receptor mediated endocytosis, transcytosis
antibody, protein, protein binding, protein sequence, thermodynamics

Institution:	ARIZEKE PHARMACEUTICALS, INC.
	6828 NANCY RIDGE DR, STE 400
	SAN DIEGO, CA 92121
Fiscal Year:	2003
Department:
Project Start:	01-AUG-2003
Project End:	31-JAN-2004
ICD:	NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
IRG:	ZRG1

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